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Comparative study of lacosamide and classical sodium channel blocking antiepileptic drugs on sodium channel slow inactivation
Author(s) -
Niespodziany Isabelle,
Leclère Nathalie,
Vandenplas Catherine,
Foerch Patrik,
Wolff Christian
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23136
Subject(s) - lacosamide , sodium channel , lamotrigine , chemistry , carbamazepine , zonisamide , phenytoin , pharmacology , sodium channel blocker , biophysics , sodium , epilepsy , neuroscience , topiramate , medicine , biology , organic chemistry
Abstract Many antiepileptic drugs (AEDs) exert their therapeutic activity by modifying the inactivation properties of voltage‐gated sodium (Na v ) channels. Lacosamide is unique among AEDs in that it selectively enhances the slow inactivation component. Although numerous studies have investigated the effects of AEDs on Na v channel inactivation, a direct comparison of results cannot be made because of varying experimental conditions. In this study, the effects of different AEDs on Na v channel steady‐state slow inactivation were investigated under identical experimental conditions using whole‐cell patch‐clamp in N1E‐115 mouse neuroblastoma cells. All drugs were tested at 100 μM, and results were compared with those from time‐matched control groups. Lacosamide significantly shifted the voltage dependence of Na v current (I Na ) slow inactivation toward more hyperpolarized potentials (by −33 ± 7 mV), whereas the maximal fraction of slow inactivated channels and the curve slope did not differ significantly. Neither SPM6953 (lacosamide inactive enantiomer), nor carbamazepine, nor zonisamide affected the voltage dependence of I Na slow inactivation, the maximal fraction of slow inactivated channels, or the curve slope. Phenytoin significantly increased the maximal fraction of slow inactivated channels (by 28% ± 9%) in a voltage‐independent manner but did not affect the curve slope. Lamotrigine slightly increased the fraction of inactivated currents (by 15% ± 4%) and widened the range of the slow inactivation voltage dependence. Lamotrigine and rufinamide induced weak, but significant, shifts of I Na slow inactivation toward more depolarized potentials. The effects of lacosamide on Na v channel slow inactivation corroborate previous observations that lacosamide has a unique mode of action among AEDs that act on Na v channels. © 2012 Wiley Periodicals, Inc.